A Pathology-based Central Tissue Resource Lab providing comprehensive tissue related services and material for investigators at Yale and beyond, including Critical Technologies for Tissue Services (CTTS).
Mission: To provide the maximum amount and quality of human tissue for research at Yale University without impacting diagnostic quality, accuracy and safety in anatomic pathology.The facility has four divisions:
Tissue Procurement and Distribution (TPD)
The TPD division of YPTS provides fresh tissue or frozen tissue in accordance with approved standard operating procedures. These SOPs are designed by investigators for specific tissue needs and then approved by the Yale Human Investigation Committee and key pathologists in the Department of Pathology. Tissues from many sources are procured prospectively. There is also a frozen tissue bank with about 5000 tissue samples. All materials are catalogued using the CaTissue software. The facility is run by Dr. Alex Vortmeyer with technical direction by Dr. Yalai Bai and her staff.
The Developmental Histology division of YPTS provides complete histology services including paraffin embedding and sectioning, frozen sections, routine and special stains, immunostaining, glycomethacrylate plastic services, development of optimized protocols for staining with non-commercial antibodies, antigen recovery techniques, custom fixation, and embedding protocols. The service also provides digital imaging services on the Bioimagene platform and is exploring offering AQUA-based quantitative immunofluorescent analysis services. The facility is run by Dr. Alex Vortmeyer with technical direction by Lori Charette and her staff.
Tissue Microarray and Archiving (TMA)
The Tissue Microarray and Archiving division of YPTS produces and analyzes tissue microarrays. This facility enables researchers to analyze several hundred formalin fixed paraffin embedded tissue samples within a single paraffin block, providing highly efficient and standardized evaluation and assessment of the samples. Tissue microarrays are in stock or can be made to order. The inventory can be found at www.tissuearray.org. The facility also oversees the Pathology Archives. The facility is run by Dr. David Rimm with technical direction by Lori Charette and her staff.
Quantitative expression analysis in tissue has a long and checkered history. Pathologists have devised numerous "semi-quantitative" grading systems that have waxed and waned in popularity. As the information capacity of computers increased, morphometric quantitative analysis became possible. Like the cDNA microarrays, the tissue microarray format lends itself to more quantitative analysis. However, tissue microarrays present some special problems that require dedicated readers, or at least dedicated software. An automated analysis protocol must not only be able to select the region of interest, but also normalize it so that the expression level read from any given disk can be compared with other disks. A related problem is that of subcellular localization. Comparisons of nuclear or membranous staining are quite different than total cytoplasmic staining. Although there are now a number of automated devices for reading tissue microarrays (Aperio, Bioimagene, ACIS, Biogenex, Applied Imaging) in our lab we use AQUA, a dedicated, automated TMA analysis software, written by Dr. Robert Camp.
Briefly, the concept behind AQUA is to use molecular, rather than feature based compartmentalization. Subcellular compartments are defined by molecular interactions using one set of fluorophores, then the protein of interest is quantified using another fluorophore within the previously defined compartments. Often Cy5, a fluorophore in the far red, is used since there is minimal tissue auto-fluorescence at this emission wavelength. Ultimately, the goal of the AQUA technology is to generate a protein concentration within a molecularly defined subcellular or architectural compartment
David Rimm, MD, PhD, Director